Category Cross-Omics>Pathway Knowledge Bases/Databases/Tools

Abstract PharmGKB (The Pharmacogenetics and Pharmacogenomics Knowledge Base) is a knowledge base (KB) that captures the relationships between drugs, diseases/phenotypes and genes involved in pharmacokinetics (PK) and pharmacodynamics (PD).

This information includes literature annotations, primary data sets, 'PK and PD pathways', and expert-generated summaries of PK/PD relationships between drugs, diseases/phenotypes and genes. PharmGKB's website is designed to effectively disseminate knowledge to meet the needs of its users.

PharmGKB has developed highly curated pathways documenting the genes involved in pharmacodynamics and pharmacokinetics of a selection of drugs.

PharmGKB currently has literature annotations documenting the relationship of over 540 drugs, 542 diseases and 1,018 variant genes.

In order to meet the needs of whole genome studies, PharmGKB has added new functionalities, including browsing the variant display by chromosome and cytogenetic locations, allowing the user to view variants Not located within a gene.

The manufacturer has developed new infrastructure for handling whole genome data, including increased methods for quality control and tools for comparison across other data sources, such as dbSNP, JSNP and HapMap data.

The manufacturer has developed an XML format for defining genotype data, a relational database schema for data storage and a flexible mechanism for submitting phenotype data.

PharmGKB has also added functionality to accept, store, display and query high throughput Single Nucleotide Polymorphism (SNP) array data.

These changes allow the manufacturer to capture more structured information on phenotypes for better cataloging and comparison of data.

PharmGKB data and knowledge are updated on a continuous basis. Access is free but requires users to register for a username and password for viewing individual subject data.

Distinguishing PharmGKB User Groups -- PharmGKB has redesigned its website homepage as well as the resource and submission tabs to more effectively disseminate knowledge in a form that matches user needs.

PharmGKB has identified four (4) main user groups of the database: gene-oriented users, drug-oriented users, bioinformaticians and clinical/disease-oriented investigators.

PharmGKB organizes knowledge pertinent to each group into user- based views and resources.

The PharmGKB homepage provides direct links to different user-based knowledge, such as drug pages or gene pages and more specifically pharmacokinetic and pharmacodynamic data.

Integrating Genomic-Scale Data -- Genetic variation is now measured on a genomic scale using SNP arrays. The successful analysis of such data sets depends on rapid access to the most current annotation of the SNPs being studied in conjunction with phenotypic data, linkage disequilibrium information and other genomic data.

Accordingly, PharmGKB has added functionality to integrate, aggregate and annotate data from genome-wide studies. These data can be queried and viewed by chromosome browsing, gene pages or individual submission pages.

VIP Gene and Variant pages -- Very Important Pharmacogenes, provide annotated information about genes, variants, haplotypes, and splice variants of particular relevance for pharmacogenetics and pharmacogenomics.

VIP gene pages highlight the key variants, haplotypes, drugs, diseases and phenotypes associated with the pharmacogene.

A VIP gene is defined as a gene that has well-documented information about its involvement in the pharmacodynamics or pharmacokinetics of a drug. There are a total of about 200 well-documented VIP genes that were selected by pharmacogenomics experts for PharmGKB to annotate.

VIP pages are hand-curated and contain information about the mapping of the variant to allow cross comparison with other resources, frequencies and drug and disease associations from key studies and the links to the literature that document them.

VIP variants link from the variant page via a flag in the row for that golden path position.

PharmGKB Pathways -- PharmGKB Pathways are drug-centered, depicting candidate genes for pharmacogenetics and pharmacogenomics studies and they provide the means to connect separate data sets to represent the current knowledge as a cohesive snapshot.

Pathways are created based on community interest and involvement/contributions. The diagrams have information content in the shape and color of the icons that represent whether the component is a gene, drug, metabolic intermediate, etc.

The pathways are interactive: clicking on a gene takes the user to the gene page from which available genotype and phenotype data and literature citations can be found. Drugs and metabolites are represented by rectangles.

Clicking on a drug takes the user to the drug page from which available phenotype data and literature citations can be found.

Clicking on a golden arrow presents the user with phenotype data that support a relationship. In addition to the pathway diagram, a summary is provided to describe the content of the graphic.

Literature Annotations -- PharmGKB has a collection of pharmaco- related literature annotations that are generated and enhanced through hand-curation.

The manufacturer allows reference addition to PharmGKB either as a Publication entry or as a Literature Annotation, which includes additional hand-curated details about the reference and the pharmacogenomic relationships described in the article.

To aid users, PharmGKB knowledge generation is achieved by combining highly searchable controlled vocabulary classifications of references with brief, detailed free-text descriptions of the primary research findings.

Phenotype Data Sets -- PharmGKB houses a variety of phenotype data sets. All phenotype submissions are accepted and PharmGKB has expanded submission methods to include Microsoft Office documents, or alternatively, a URL to another established archival public database (e.g. GEO - see G6G Abstract Number 20013).

High-impact phenotype data sets are curated by hand, while others receive minimal oversight at PharmGKB.

High-impact phenotype data sets correspond to genotype data submitted to PharmGKB and are typically published in peer-review journals.

These data are featured on the PharmGKB website with an interactive display, curated annotations and downloadable Excel files.

All phenotype files on PharmGKB are fully text-searchable. PharmGKB also offers links to web sites with controlled vocabularies in order to encourage investigators to optimize documentation of their deposits.

Note: For all data sets in PharmGKB, genes, drugs, diseases and categories of pharmacogenetic evidence are tagged and indexed for querying.

System Requirements



Manufacturer Web Site PharmGKB

Price Free

G6G Abstract Number 20304

G6G Manufacturer Number 102513